The present invention relates to drug delivery systems, and more particularly, to a mechanical device that alters the outermost layer of skin for the improved delivery of compounds through the skin.
Transdermal delivery of medication is well known in the prior art. Transdermal patches are available for a number of drugs. Commercially available examples of transdermal patches include scopolamine for the prevention of motion sickness, nicotine for aid in smoking cessation, nitroglycerin for the treatment of coronary angina pain, and estrogen for hormonal replacement. Generally, these systems have drug reservoirs sandwiched between an impervious backing and a membrane face which controls the steady state rate of drug delivery. The systems usually are attached to the skin by an adhesive gel with the membrane face adjacent to the skin.
Transdermal medication has significant advantages over both hypodermic injection and oral administration. A transdermal patch can provide significantly greater effective blood levels of a beneficial drug because the drug is not delivered in spike concentrations as is the case with hypodermic injection and most oral administration. In addition, drugs administered via transdermal patches are not subjected to the harsh environment of the digestive tract. Hence, in principle, transdermal delivery provides a method for administrating drugs that would otherwise need to be administered via hypodermic injection or intravenous infusion because the drug is destroyed in the digestive tract or immediately absorbed by the liver. Conversely, the digestive tract and liver are not subjected to the drug in transdermal administration. Many drugs, such as aspirin, have an adverse effect on the digestive tract.
Prior art transdermal drug delivery systems may be divided into passive diffusion and active transport systems. Transdermal drug delivery by diffusion is by far the most common of the transdermal methods. The nicotine patch is an example of this method of delivery (U.S. Pat. No. 4,597,961 to Frank T. Etscorn). This process is based on presenting the medication in a high dose external to the dermis and allowing the chemical to diffuse into and through the skin. The degree of diffusion depends on the porosity of the skin, the size and polarity of the drug molecules, and the concentration gradient across the stratum corneum, the outermost layer of human skin. These factors generally limit this mode of delivery to a very small number of useful drugs with very small molecules or unique electrical characteristics.
There have been two types of systems proposed to overcome the limited range of compounds that may be administered transdermally. The first class of techniques are based on the disruption of the skin to remove the diffusion barrier. One such method is described in U.S. Pat. No. 3,964,482. This technique utilizes an array of needle like protrusions that penetrate the stratum corneum. The drug is delivered either through the needles or on the surface of the skin. In the this case, the drug flows along the outer surface of the xe2x80x9cneedlexe2x80x9d through the hole in the stratum corneum created by the needle. The length of the needles utilized in this invention is just long enough to penetrate the stratum corneum. Since the stratum corneum does not contain blood vessels or nerve endings, the patient does not experience bleeding or discomfort from the penetration of the needles.
While this device has been known for over 25 years, devices of this type have not been commercially successful. The disruption of the stratum corneum is not sufficient to render the skin sufficiently permeable to allow many compounds of interest to be administered transdermally.
Attempts to widen the range of drugs that may be transdermally delivered have also led to the active methods mentioned above. The active diffusion systems involve iontophoresis, electroporation, and ultrasound to increase the migration of the drug across the skin barrier. These methods attempt to electrically assist diffusion of the medication or apply high frequency electrical pulses or soundwaves to the skin to improve absorption. Unfortunately, the high cost and inconvenience of providing portable electrical equipment have limited the commercial application of such active systems.
Accordingly, it is a general object of the present invention to provide an improved transdermal drug delivery system and method.
It is another object of the invention to eliminate or greatly reduce the pain of drug delivery by present skin-penetrating devices, such as needles, fluid jets, iontophoresis, etc.
It is another object of the present invention to provide a transdermal delivery system that does not rely on applied electric fields, yet allows drugs that could not previously be administered by passive diffusion to be so administered.
These and other objects of the present invention will become apparent to those skilled in the art from the following detailed description of the invention and the accompanying drawings.
The present invention comprises a drug delivery system including an apparatus for mechanically disrupting a layer of skin having a known thickness without substantially disrupting underlying dermis layers below the layer of skin in question and a reservoir for continuously applying the drug to the disrupted area of skin. The apparatus includes a cutter having a plurality of microprotrusions having a height chosen with respect to the layer of skin that is to be disrupted and a stop for preventing the apparatus from penetrating the skin beyond a predetermined distance. In the preferred embodiment of the present invention, the microprotrusions include blades that generate cuts in the layer of skin. The cuts are generated by moving the apparatus parallel to the surface of the skin either at the time of application, during the normal movements of the individual wearing the apparatus, or both. In the preferred embodiment of the present invention, the appropriate length of blade is determined for each individual and delivery site on that individual.